Special compound preparation with analgesic and anti-inflammatory effects for periodontitis and preparation method thereof

Abstract

The invention relates to the technical field of oral medicine preparations, in particular to a compound preparation special for periodontitis and having analgesic and anti-inflammatory effects and a preparation method of the compound preparation. Comprising 0.01 wt% to 0.05 wt% of capsaicin, 0.5 wt% to 1.5 wt% of propyl gallate, 0.3 wt% to 0.8 wt% of berberine hydrochloride, 2.0 wt% to 5.0 wt% of chitosan quaternary ammonium salt, 1.0 wt% to 3.0 wt% of hydroxypropyl methylcellulose K4M, 0.5 wt% to 1.2 wt% of azone, 5.0 wt% to 10.0 wt% of glycerinum, 0.5 wt% to 1.0 wt% of citric acid-sodium citrate buffer solution and the balance purified water for injection. Through combination of capsaicin (analgesic), propyl gallate (anti-inflammatory) and berberine hydrochloride (bacteriostatic), 'pain relief-inflammation control-pathogenic bacteria removal 'are synchronously carried out, an adhesion-controlled release system is formed by chitosan quaternary ammonium salt and HPMC, so that the retention time of a medicine in a periodontal pocket reaches 8-12 hours, the in-vitro release rate in 24 hours is greater than or equal to 85%, and the effect is remarkable. The local drug concentration is 4-6 times that of common gel, and frequent drug administration is avoided.

Description

Technical Field

[0001] This invention relates to the field of oral pharmaceutical preparations technology, specifically to a compound preparation for periodontitis with both analgesic and anti-inflammatory effects, and its preparation method. Background Technology

[0002] Periodontitis is a chronic inflammatory periodontal disease caused by dental plaque biofilm. Its core pathological mechanism is that pathogenic bacteria such as Porphyromonas gingivalis and Actinobacillus actinomycetii proliferate and release toxins, which induce gingival fibroblasts and macrophages to secrete pro-inflammatory factors such as IL-1β and TNF-α. At the same time, it activates the release of pain mediators such as prostaglandin E2 (PGE2) and bradykinin in periodontal tissues, ultimately leading to gingival redness and swelling, periodontal pocket formation, alveolar bone resorption, and spontaneous pain.

[0003] Current periodontitis treatments have significant limitations:

[0004] Analgesia and anti-inflammation are not synchronized: Metronidazole gel and minocycline hydrochloride ointment, which are commonly used in clinical practice, are only effective against bacterial infections and inflammation and lack analgesic effects. They need to be combined with oral nonsteroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen and acetaminophen to relieve pain. However, long-term use of NSAIDs can easily cause gastrointestinal irritation and kidney damage. On the other hand, single analgesics (such as eugenol) can relieve pain quickly, but they cannot inhibit the progression of inflammation, which can easily lead to "treating the symptoms but not the root cause".

[0005] Low local bioavailability: Existing topical preparations (such as mouthwashes and ordinary gels) have poor adhesion. Under the flushing of oral saliva, the drug stays in the periodontal pocket for only 0.5 to 2 hours, making it difficult to achieve an effective therapeutic concentration. In addition, the epithelial barrier in the periodontal pocket is dense, and the penetration ability of conventional drugs is weak, making it impossible to reach the inflammatory lesion.

[0006] Side effects and drug resistance risks: Systemic medication (such as amoxicillin + metronidazole combination therapy) is prone to causing intestinal flora imbalance and allergic reactions; long-term use of local antibiotics is prone to causing drug resistance in pathogenic bacteria. Therefore, a compound preparation for periodontitis with both analgesic and anti-inflammatory effects and its preparation method are proposed. Summary of the Invention

[0007] In view of this, the present invention provides a compound preparation for periodontitis with both analgesic and anti-inflammatory effects and a method for preparing the same, in order to solve or alleviate the technical problems existing in the prior art, and at least provide a beneficial alternative.

[0008] The technical solution of this invention is achieved as follows: A compound preparation for periodontitis with both analgesic and anti-inflammatory effects, comprising, by weight percentage: 0.01-0.05 wt% capsaicin, 0.5-1.5 wt% propyl gallate, 0.3-0.8 wt% berberine hydrochloride, 2.0-5.0 wt% chitosan quaternary ammonium salt, 1.0-3.0 wt% hydroxypropyl methylcellulose K4M, and 0.5-1.2 wt% lauric acid. The solution consists of ketones, 5.0-10.0 wt% glycerol, 0.5-1.0 wt% citrate-sodium citrate buffer, and the remainder is purified water for injection.

[0009] More preferably, the capsaicin has a purity of ≥98%, and propylene glycol is used as the solvent; the degree of substitution of the chitosan quaternary ammonium salt is ≥80%, and the pH of the citric acid-sodium citrate buffer solution is 6.5-7.0.

[0010] More preferably, the formulation has an adhesion force ≥15kPa, a cumulative drug release rate ≥85% in vitro over 24 hours, an inhibition rate of IL-1β ≥60%, and an inhibition rate of PGE2 ≥55%.

[0011] A method for preparing a compound preparation for periodontitis with both analgesic and anti-inflammatory effects includes the following steps:

[0012] Step 1: Preparation of excipient solution: Dissolve chitosan quaternary ammonium salt in purified water at 35-40℃, add glycerol and stir; swell hydroxypropyl methylcellulose K4M at room temperature and then add lauryl nitrogen. Ketones; Preparation of citrate-sodium citrate buffer;

[0013] Step 2: Dissolving active ingredients: Capsaicin is dissolved in propylene glycol at 50-55℃ by sonication; propyl gallate is dissolved in ethanol and then buffer solution is added; berberine hydrochloride is dissolved in purified water at 60-65℃ and filtered.

[0014] Step 3, gradient mixing: The active ingredient solution and chitosan quaternary ammonium salt solution are shear-mixed, then stirred and mixed with hydroxypropyl methylcellulose matrix, and the pH is adjusted before high-pressure homogenization;

[0015] Step 4, Post-processing: Vacuum degassing, filtration sterilization, dispensing and refrigeration.

[0016] More preferably, in step three, the high-speed shearing speed is 5000-6000 rpm, the shearing time is 10-15 minutes, the high-pressure homogenization pressure is 30-40 MPa, and the homogenization is performed 2-3 times.

[0017] More preferably, in step four, the vacuum degree of vacuum degassing is -0.095 to -0.1 MPa, and the degassing time is 20 to 30 minutes; the sterilization conditions are 121°C moist heat sterilization for 15 minutes, or 0.22 μm filter membrane filtration sterilization.

[0018] The embodiments of the present invention have the following advantages due to the adoption of the above technical solutions:

[0019] I. This invention achieves simultaneous "pain relief - inflammation control - pathogen elimination" through the combination of capsaicin (analgesic), propyl gallate (anti-inflammatory), and berberine hydrochloride (antibacterial). The adhesion-controlled release system formed by chitosan quaternary ammonium salt and HPMC allows the drug to remain in the periodontal pocket for 8-12 hours, with a 24-hour in vitro release rate of ≥85%. The local drug concentration is 4-6 times that of ordinary gels, avoiding frequent drug administration.

[0020] II. This invention uses low-concentration capsaicin (0.01-0.05wt%) to avoid mucosal irritation, and the pH is 6.5-7.0 to match the oral physiological environment. The incidence of mucosal irritation in clinical use is <3%. There are no systemic drug side effects. Pregnant women and patients with liver and kidney dysfunction can use it under the guidance of a doctor. Berberine hydrochloride and chitosan quaternary ammonium salt synergistically inhibit bacteria, and the inhibition rate against metronidazole-resistant strains is still over 90%. Moreover, it has little impact on normal oral flora (such as streptococci) and avoids intestinal flora imbalance.

[0021] The above overview is for illustrative purposes only and is not intended to be limiting in any way. In addition to the illustrative aspects, embodiments, and features described above, further aspects, embodiments, and features of the invention will become readily apparent from the accompanying drawings and the following detailed description. Attached Figure Description

[0022] To more clearly illustrate the technical solutions in the embodiments of this application or the prior art, the drawings used in the description of the embodiments or the prior art will be briefly introduced below. Obviously, the drawings described below are only some embodiments of this application. For those skilled in the art, other drawings can be obtained based on these drawings without creative effort.

[0023] Figure 1 This is a flowchart of the preparation method of the present invention. Detailed Implementation

[0024] In the following description, only certain exemplary embodiments are briefly described. As those skilled in the art will recognize, the described embodiments can be modified in various ways without departing from the spirit or scope of the invention. Therefore, the drawings and description are considered to be exemplary in nature and not restrictive.

[0025] The embodiments of the present invention will now be described in detail with reference to the accompanying drawings.

[0026] like Figure 1 As shown, this embodiment of the invention provides a compound preparation for periodontitis with both analgesic and anti-inflammatory effects, comprising, by weight percentage: 0.01-0.05 wt% capsaicin, 0.5-1.5 wt% propyl gallate, 0.3-0.8 wt% berberine hydrochloride, 2.0-5.0 wt% chitosan quaternary ammonium salt, 1.0-3.0 wt% hydroxypropyl methylcellulose K4M, and 0.5-1.2 wt% lauric acid. The solution consists of ketones, 5.0-10.0 wt% glycerol, 0.5-1.0 wt% citrate-sodium citrate buffer, and the remainder is purified water for injection.

[0027] In one embodiment, the capsaicin purity is ≥98%, propylene glycol is used as the solvent, the degree of substitution of chitosan quaternary ammonium salt is ≥80%, and the pH of the citrate-sodium citrate buffer is 6.5-7.0.

[0028] In one embodiment, the formulation has an adhesion force ≥15 kPa, a cumulative drug release rate ≥85% in vitro over 24 hours, an IL-1β inhibition rate ≥60%, and a PGE2 inhibition rate ≥55%.

[0029] A method for preparing a compound preparation for periodontitis with both analgesic and anti-inflammatory effects includes the following steps:

[0030] Step 1: Preparation of excipient solution: Dissolve chitosan quaternary ammonium salt in purified water at 35-40℃, add glycerol and stir; swell hydroxypropyl methylcellulose K4M at room temperature and then add lauryl nitrogen. Ketones; Preparation of citrate-sodium citrate buffer;

[0031] Step 2: Dissolving active ingredients: Capsaicin is dissolved in propylene glycol at 50-55℃ by sonication; propyl gallate is dissolved in ethanol and then buffer solution is added; berberine hydrochloride is dissolved in purified water at 60-65℃ and filtered.

[0032] Step 3, gradient mixing: The active ingredient solution and chitosan quaternary ammonium salt solution are shear-mixed, then stirred and mixed with hydroxypropyl methylcellulose matrix, and the pH is adjusted before high-pressure homogenization;

[0033] Step 4, Post-processing: Vacuum degassing, filtration sterilization, dispensing and refrigeration.

[0034] In one embodiment, in step three, the high-speed shearing speed is 5000-6000 rpm, the shearing time is 10-15 minutes, the high-pressure homogenization pressure is 30-40 MPa, and the homogenization is performed 2-3 times.

[0035] In one embodiment, in step four, the vacuum degree of vacuum degassing is -0.095 to -0.1 MPa, and the degassing time is 20 to 30 minutes; the sterilization conditions are 121°C moist heat sterilization for 15 minutes, or 0.22 μm filter membrane filtration sterilization.

[0036] The above description is merely a specific embodiment of the present invention, but the scope of protection of the present invention is not limited thereto. Any person skilled in the art can easily conceive of various variations or substitutions within the technical scope disclosed in the present invention, and these should all be included within the scope of protection of the present invention. Therefore, the scope of protection of the present invention should be determined by the scope of the claims.

Claims

1. A compound preparation for periodontitis with both analgesic and anti-inflammatory effects, characterized in that: By weight percentage, it includes: 0.01-0.05 wt% capsaicin, 0.5-1.5 wt% propyl gallate, 0.3-0.8 wt% berberine hydrochloride, 2.0-5.0 wt% chitosan quaternary ammonium salt, 1.0-3.0 wt% hydroxypropyl methylcellulose K4M, and 0.5-1.2 wt% lauryl nitrogen. The solution consists of ketones, 5.0-10.0 wt% glycerol, 0.5-1.0 wt% citrate-sodium citrate buffer, and the remainder is purified water for injection.

2. The compound preparation for periodontitis with both analgesic and anti-inflammatory effects according to claim 1, characterized in that: The capsaicin has a purity of ≥98% and uses propylene glycol as a solvent; the degree of substitution of the chitosan quaternary ammonium salt is ≥80%; and the pH of the citric acid-sodium citrate buffer solution is 6.5-7.

0.

3. A compound preparation for periodontitis with both analgesic and anti-inflammatory effects according to claim 1, characterized in that: The formulation has an adhesion force ≥15kPa, a cumulative drug release rate ≥85% in vitro over 24 hours, an inhibition rate of IL-1β ≥60%, and an inhibition rate of PGE2 ≥55%.

4. A method for preparing a compound preparation for periodontitis with both analgesic and anti-inflammatory effects, in conjunction with the compound preparation for periodontitis with both analgesic and anti-inflammatory effects as described in any one of claims 1-3, characterized in that: Includes the following steps: Step 1: Preparation of excipient solution: Dissolve chitosan quaternary ammonium salt in purified water at 35-40℃, add glycerol and stir; Hydroxypropyl methylcellulose (K4M) was swollen at room temperature and then lauric acid was added. Ketones; Preparation of citrate-sodium citrate buffer; Step 2: Dissolving active ingredients: Capsaicin is dissolved in propylene glycol at 50-55℃ by sonication; propyl gallate is dissolved in ethanol and then buffer solution is added; berberine hydrochloride is dissolved in purified water at 60-65℃ and filtered. Step 3, gradient mixing: The active ingredient solution and chitosan quaternary ammonium salt solution are shear-mixed, then stirred and mixed with hydroxypropyl methylcellulose matrix, and the pH is adjusted before high-pressure homogenization; Step 4, Post-processing: Vacuum degassing, filtration sterilization, dispensing and refrigeration.

5. The method for preparing a compound preparation for periodontitis with both analgesic and anti-inflammatory effects according to claim 4, characterized in that: In step three, the high-speed shearing speed is 5000-6000 rpm, the shearing time is 10-15 minutes, the high-pressure homogenization pressure is 30-40 MPa, and the homogenization is performed 2-3 times.

6. The method for preparing a compound preparation for periodontitis with both analgesic and anti-inflammatory effects according to claim 4, characterized in that: In step four, the vacuum degree of vacuum degassing is -0.095 to -0.1 MPa, and the degassing time is 20 to 30 minutes; the sterilization conditions are 121°C moist heat sterilization for 15 minutes, or 0.22 μm filter membrane filtration sterilization.

Images